Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints which leads to joint destruction, disability and early death. Although the cause of RA is presently unknown, it has been suggested that type II collagen, uniquely found in the articular cartilage, is a possible autoantigen for RA. It has recently been proposed that gp39, a 39 KD glycoprotein, and peptides derived from it, are such autoantigens. However, the data supporting this hypothesis are limited and the role of gp39 therefore remains uncertain.
The present invention stems from a different approach based on a study of chondrocytes, the specialised cells of articular cartilage. We have isolated a protein from human chondrocytes and human chondrosarcoma cell lines which reacts with antibodies present in RA patients' sera and meets the accepted criteria for a putative autoantigen. This purified protein has been tested for proliferation of T cells and has been shown to selectively proliferate synovial T cells from patients with RA. This protein is the immunoglobulin heavy chain binding protein BiP(78 KD).
International patent application WO 99/18131 proposes the detection of antibodies to a BiP deriving from Hela cells as a diagnostic indication of RA. However, this prior disclosure does not describe the extraction of BiP from the Hela cells in a reproducible manner and is therefore insufficient for practical application.